The present invention relates to novel compositions comprising stinging cells or capsules and methods of using same.
Keratin is a fibrous protein that serves as a structural unit for various living tissues. Keratin is the major protein component of hair, wool, nails, horn, hoofs, and the quills of feathers. It contains large quantities of the sulfur-containing amino acids, particularly cysteine. The formation of a disulfide bridge between the sulfur atoms on two cysteines on separate polypeptide chains of keratin allows for the cross-linkage of these chains and results in a fairly rigid aggregate. This phenomenon is consistent with the physiological role of keratin, which provides a tough, fibrous matrix for the tissues in which it is found.
Anatomically, hair comprises three layers, namely, the medulla, cortex and cuticle. The cuticle is the outermost surface of the hair shaft and is composed of a very hard keratinous substance. It consists of flattened platelets of amorphous keratin, wrapped around the hair shaft in several layers, each layer overlapping the adjacent one, progressing from the root to the tip of the hair. A cross section of each cuticle scale reveals that it is sub-divided into three further layers, the endocuticle, exocuticle and epicuticle respectively, the latter one being the outermost layer.
The medulla is the innermost layer of the hair and is composed of a soft keratin-rich material and its occurrence in human hair appears to be variable, usually being present in large thick hairs. Lastly, the cortex is the inner bulk of the hair, which forms the main body of the hair. The cortex is disposed between the medulla and the cuticle. It is composed of a soft, fibrous, crystalline keratin. It provides strength, color and texture to the hair.
Long-lasting treatment of hair requires that therapeutic and cosmetic agents traverse the cuticle and penetrate the cortex in order to react with the keratin inside it and the medulla. Typically, this is achieved by increasing the temperature, or application of an alkaline lotion such as ammonia, both of which serve to separate the scales of the cuticle enough to allow the chemicals to pass through. After the treatment is finished the scales gradually close up again.
However, if hair is processed too many times the cuticle scales may never return to their original tightness and the protection they once offered is lost. The hair becomes increasingly porous, and water can then pass in and out of the cortex. Over-porous hair is dry, and tends to develop split ends. The damaged cuticle is fragile, and the damage worsens as time goes by. The greater the damage, the more the cortex swells with water whenever the hair is washed, but the more water it loses when it dries. The repeated wetting and drying of the cortex gradually weakens the hair.
Ammonia has an additional disadvantageous since it is a reducing agent and breaks sulfur bridges inside the hair. The elasticity of the hair is dependent on a particular sum of sulfur bridges so that if the ammonia treatment is too harsh, the hair will lose more sulfur bonds than necessary causing the hair to harden, lose weight and diameter.
Anti-parasitic agents used to treat the hair are generally provided topically and are rinsed out with water. Thus, their toxic effects last only for the amount of time that the agents are left in the hair. Recurrence of infection is high since it is very difficult to kill all the parasites at all stages of their life cycle.
Fungal infections of the nail are common throughout the world. An estimated 2-13% of the population is affected in North America, with at least 15-20% of those aged 40-60 having one or more fingernails or toenails infected. Toenails are much more commonly affected than fingernails. Infections can range from superficial, causing little more than discoloration, to severe, resulting in loss of the nail together with deformities of the surrounding digit. The incidence of nail fungal infections has been rising over the past few decades, due to factors such as an increased elderly population, increased participation in vigorous physical activity while wearing moisture-retaining shoes and socks, an increase in the number of HIV infected individuals, an increased incidence of diabetes, and increased use of steroids, antibiotics, and other therapeutics that can suppress immunologic responses to fungi.
While nail fungus is rarely life threatening, it causes significant pain, inconvenience, embarrassment, emotional distress, and limitations to manual performance and ambulation. Individuals with moderate to severe nail fungal infections can lose their ability to perform many routine tasks (such as fastening buttons, picking up small objects, walking significant distances) and can lose the ability to perform satisfactorily in their occupations. Due to the unpleasant appearance of their hands or feet, these individuals may become socially self-conscious and embarrassed, and may avoid intimate or other close contact with people. Loss of self-esteem, anxiety, and depression commonly result from moderate to severe cases of fungal nail infection.
At present, topical treatments for nail fungus are rarely effective. Although some oral antifungal therapies have moderate efficacy, they also pose significant risks of toxic reactions, and many patients would prefer local treatments to systemic treatments.
There thus remains a need for improved methods and devices for delivery of therapeutic and cosmetic agents into keratinous substances such as the hair and nail.
“Stinging cells” (e.g. cnidocytes, nematocytes and the like) or “stinging capsules” (e.g., cnidocysts, nematocysts and polar capsules) isolated therefrom have been proposed as suitable agents for tissue delivery of a therapeutic or cosmetic agents [U.S. Pat. Nos. 6,923,976 and 6,613,344 and U.S. Pat. App. No. 20040224013]. Cnidaria (hydras, sea anemones, jellyfish and corals) are aquatic animals, which possess a variety of compounds which are stored and delivered via specialized capsules (cnidocysts), which form a part of specialized cells termed stinging cells (cnidocytes, nematocytes, ptychocytes and the like). The stinging capsules are hard and dense and filled with liquid containing a highly folded, inverted tubule which may also feature specialized structures such as shafts, barbs, spines, and/or stylets. In nature, the cnidocyst discharges and releases its tubule into tissue following physical or chemical triggering.
Discharge is initiated by a rapid osmotic influx of water which generates an internal hydrostatic (liquid) pressure of 150 atmospheres forcing capsule rupture and ejection of the tubule [Holstein, T., and Tardent, P. (1984)Science, 223(4638), 830-3]. During ejection, the long coiled and twisted tubule is averted and its length increases by 95%. Accelerating at 40,000 g, the tubule untwists to generate a torque force, which rotates the tubule several times around its axis. These mechanical processes generate a powerful driving force, which enables efficient delivery of the compounds, the toxins and enzymes stored within the capsule [Lotan et al., 1995 Nature, 375(6531), 456: Lotan et al., 1996 J Exp Zool, 275(6), 444-51; Tardent 1995, BioEssays, 17(4), 351-362]. This process, which occurs within microseconds, is among the most rapid exocytosis events in biology [Holstein, T., and Tardent, P. (1984) Science, 223(4638), 830-3].
The Cnidaria family which encompasses 10,000 known species includes sedentary single or colonial polyps and pelagic jellyfish. In some of these species, cnidocytes account for more than 45% of the cells present [Tardent 1995, BioEssays, 17(4), 351-362].
There are at least three dozen known types of cnidocysts (also termed cnidae) including more than 30 varieties of nematocysts found in most Cnidaria and spirocysts, and ptychocysts found mainly in the Cnidaria class Anthozoa [Mariscal 1974, Coelenterate biology: reviews and new perspectives, Academic Press, New York.].
U.S. Pat. Appl. No. 20040224013 and U.S. Pat. Nos. 6,923,976 and 6,613,344 to the present author teach use of stinging cells for in vivo administration of an active agent into the hair follicle via the skin of the scalp and into the nail via the skin of the cuticle. Penetration of living skin tissue, as taught by U.S. Pat. Appl. No. 20040224013 and U.S. Pat. Nos. 6,923,976 and 6,613,344, as opposed to the dead cells of the hair shaft or nail, limits the number of active agents which may be used. Furthermore, for local treatment it is preferred not to treat the skin as the active agents may enter the systemic circulation thereby increasing the incidence of adverse side effects. Penetration into the skin may also be associated with pain. In addition, some treatments, such as hair dyes and anti-parasitic, anti insect agents are not effective when delivered via the skin.
There is thus a widely recognized need for, and it would be highly advantageous to have a non-harmful and non-invasive method of treating keratinous substances such as hair and nails.